The Experts below are selected from a list of 873 Experts worldwide ranked by ideXlab platform

Zbigniew K Wszolek - One of the best experts on this subject based on the ideXlab platform.

  • DCTN1 related neurodegeneration perry syndrome and beyond
    Parkinsonism & Related Disorders, 2017
    Co-Authors: Takuya Konno, Owen A Ross, Helio A G Teive, Jaroslaw Slawek, Dennis W Dickson, Zbigniew K Wszolek
    Abstract:

    Abstract Perry syndrome (PS) is a rare hereditary neurodegenerative disease characterized by autosomal dominant parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and distinct TDP-43 pathology. The mutated causative gene for PS is DCTN1, which encodes the dynactin subunit p150Glued. Dynactin is a motor protein involved in axonal transport; the p150Glued subunit has a critical role in the overall function. Since the discovery of DCTN1 in PS, it has been increasingly recognized that DCTN1 mutations can exhibit more diverse phenotypes than previously thought. Progressive supranuclear palsy- and/or frontotemporal dementia-like phenotypes have been associated with the PS phenotypes. In addition, DCTN1 mutations were identified in a family with motor-neuron disease before the discovery in PS. In this review, we analyze the clinical and genetic aspects of DCTN1-related neurodegeneration and discuss its pathogenesis. We also describe three families with PS, Canadian, Polish, and Brazilian. DCTN1 mutation was newly identified in two of them, the Canadian and Polish families. The Canadian family was first described in late 1970’s but was never genetically tested. We recently had the opportunity to evaluate this family and to test the gene status of an affected family member. The Polish family is newly identified and is the first PS family in Poland. Although still rare, DCTN1-related neurodegeneration needs to be considered in a differential diagnosis of parkinsonian disorders, frontotemporal dementia, and motor-neuron diseases, especially if there is family history.

  • Perry Syndrome: A Distinctive Type of TDP-43 Proteinopathy.
    Journal of Neuropathology and Experimental Neurology, 2017
    Co-Authors: Takayasu Mishima, Yoshio Tsuboi, Zbigniew K Wszolek, Shunsuke Koga, Koji Kasanuki, Monica Castanedes-casey, Shin J. Oh, Dennis W Dickson
    Abstract:

    Perry syndrome is a rare atypical parkinsonism with depression, apathy, weight loss, and central hypoventilation caused by mutations in dynactin p150glued (DCTN1). A rare distal hereditary motor neuropathy, HMN7B, also has mutations in DCTN1. Perry syndrome has TAR DNA-binding protein of 43 kDa (TDP-43) inclusions as a defining feature. Other TDP-43 proteinopathies include amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with and without motor neuron disease (FTLD-MND). TDP-43 forms aggregates in neuronal cytoplasmic inclusions (NCIs), neuronal intranuclear inclusions, dystrophic neurites (DNs), as well as axonal spheroids, oligodendroglial cytoplasmic inclusions, and perivascular astrocytic inclusions (PVIs). We performed semiquantitative assessment of these lesions and presence of dynactin subunit p50 lesions in 3 cases of Perry syndrome and one of HMN7B. We compared them with 3 cases of FTLD-MND, 3 of ALS, and 3 of hippocampal sclerosis (HpScl). Perry syndrome had NCIs, DNs, and frequent PVIs and spheroids. Perry syndrome cases were similar, but different from ALS, FTLD-MND, and HpScl. TDP-43 pathology was not detected in HMN7B. Dynactin p50 inclusions were observed in both Perry syndrome and HMN7B, but not in the other conditions. These results suggest that Perry syndrome may be distinctive type of TDP-43 proteinopathy.

  • in vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers
    Movement Disorders, 2014
    Co-Authors: Andre C Felicio, Zbigniew K Wszolek, Katherine Dinelle, Pankaj Agarwal, Jessamyn Mckenzie, Nicole Heffernan, Jeremy Road, Silke Appelcresswell, Matthew J Farrer, Michael Schulzer
    Abstract:

    Introduction We used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome. Methods All subjects had brain imaging using 18F-6-fluoro-l-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter). Results FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate, and left ventral striatum. Conclusions Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene. © 2014 International Parkinson and Movement Disorder Society

  • DCTN1 mutations and progressive supranuclear palsy like phenotype
    JAMA Neurology, 2014
    Co-Authors: Shinsuke Fujioka, Pawel Tacik, Zbigniew K Wszolek
    Abstract:

    outsintheringorconcussionsontheplayingfieldonlytocom-peteandexcelatthehighestechelonofhisorherchosensport?DrCantuisindeedrightwhenhestressestheneedforfurtherevidence-based research in this area. One size does not fit allwhenitcomestoreturntoplayvspermanentretirementdeci-sionsinpatientswithconcussion.Nitin K. Sethi, MD

  • DCTN1 Mutations and Progressive Supranuclear Palsy–Like Phenotype
    JAMA Neurology, 2014
    Co-Authors: Shinsuke Fujioka, Pawel Tacik, Zbigniew K Wszolek
    Abstract:

    outsintheringorconcussionsontheplayingfieldonlytocom-peteandexcelatthehighestechelonofhisorherchosensport?DrCantuisindeedrightwhenhestressestheneedforfurtherevidence-based research in this area. One size does not fit allwhenitcomestoreturntoplayvspermanentretirementdeci-sionsinpatientswithconcussion.Nitin K. Sethi, MD

Agnes Camuzat - One of the best experts on this subject based on the ideXlab platform.

  • DCTN1 mutation analysis in families with progressive supranuclear palsy like phenotypes
    JAMA Neurology, 2014
    Co-Authors: Paola Caroppo, Fabienne Clot, Sophie Rivaudpechoux, Agnes Camuzat
    Abstract:

    Importance Progressive supranuclear palsy (PSP) is usually sporadic, but few pedigrees with familial clustering of PSP-like phenotypes have been described. Occasionally, MAPT, C9ORF72 , and TARDBP mutations have been identified. Objective To analyze the DCTN1 gene in 19 families with a clinical phenotype of PSP (PSP-like phenotype). Design, Setting, and Participants Sequencing of the DCTN1 gene in familial forms of PSP at a referral center among 21 patients with familial PSP-like phenotypes. In addition, 8 patients and relatives from a family carrying a DCTN1 mutation were evaluated. Main Outcomes and Measures Identification of the DCTN1 mutation and clinical description of DCTN1 mutation carriers. Results We identified a DCTN1 mutation in a large family characterized by high intrafamilial clinical phenotype variability. Two patients had PSP-like phenotypes with dystonia, vertical gaze slowness, dysexecutive syndrome, predominant axial rigidity, and midbrain atrophy on brain magnetic resonance imaging. The other patients manifested Perry syndrome, isolated parkinsonism, or a predominant behavioral variant of frontotemporal dementia. Conclusions and Relevance Mutations of the DCTN1 gene have been previously associated with amyotrophic lateral sclerosis and with Perry syndrome, a rare autosomal dominant disorder characterized by weight loss, parkinsonism, central hypoventilation, and psychiatric disturbances. Our study demonstrates that DCTN1 mutations should be searched for in patients with clinical PSP-like phenotypes and a behavioral variant of frontotemporal dementia, especially when a familial history of dementia, psychiatric disturbances, associated parkinsonism, or an autosomal dominant disorder is present.

Paola Caroppo - One of the best experts on this subject based on the ideXlab platform.

  • DCTN1 mutation analysis in families with progressive supranuclear palsy like phenotypes
    JAMA Neurology, 2014
    Co-Authors: Paola Caroppo, Fabienne Clot, Sophie Rivaudpechoux, Agnes Camuzat
    Abstract:

    Importance Progressive supranuclear palsy (PSP) is usually sporadic, but few pedigrees with familial clustering of PSP-like phenotypes have been described. Occasionally, MAPT, C9ORF72 , and TARDBP mutations have been identified. Objective To analyze the DCTN1 gene in 19 families with a clinical phenotype of PSP (PSP-like phenotype). Design, Setting, and Participants Sequencing of the DCTN1 gene in familial forms of PSP at a referral center among 21 patients with familial PSP-like phenotypes. In addition, 8 patients and relatives from a family carrying a DCTN1 mutation were evaluated. Main Outcomes and Measures Identification of the DCTN1 mutation and clinical description of DCTN1 mutation carriers. Results We identified a DCTN1 mutation in a large family characterized by high intrafamilial clinical phenotype variability. Two patients had PSP-like phenotypes with dystonia, vertical gaze slowness, dysexecutive syndrome, predominant axial rigidity, and midbrain atrophy on brain magnetic resonance imaging. The other patients manifested Perry syndrome, isolated parkinsonism, or a predominant behavioral variant of frontotemporal dementia. Conclusions and Relevance Mutations of the DCTN1 gene have been previously associated with amyotrophic lateral sclerosis and with Perry syndrome, a rare autosomal dominant disorder characterized by weight loss, parkinsonism, central hypoventilation, and psychiatric disturbances. Our study demonstrates that DCTN1 mutations should be searched for in patients with clinical PSP-like phenotypes and a behavioral variant of frontotemporal dementia, especially when a familial history of dementia, psychiatric disturbances, associated parkinsonism, or an autosomal dominant disorder is present.

Prasad Iyer - One of the best experts on this subject based on the ideXlab platform.

C Munch - One of the best experts on this subject based on the ideXlab platform.

  • the p150 subunit of dynactin DCTN1 gene in multiple sclerosis
    Acta Neurologica Scandinavica, 2007
    Co-Authors: C Munch, Thomas Meyer, R Meyer, P Linke, Albert C Ludolph, Judith Haas, B Hemmer
    Abstract:

    Objectives –  Mutations in the p150 subunit of the axonal transport protein dynactin (DCTN1) have been reported in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Given the common features of neurodegeneration in multiple sclerosis (MS), FTD and ALS, sequence variants of the DCTN1 gene may be a contributory factor to neurodegeneration in MS. Methods –  We investigated a total of 200 MS patients and 200 controls. A total of 100 patients had a relapsing–remitting form of MS, 100 cases were primary progressive. Sequence alterations were screened for in the coding region of DCTN1 using heteroduplex and sequence analyses. Results –  Two heterozygous missense mutations (T1249I, I196V) were found in two healthy control subjects. No mutations were identified in 200 MS patients. The frequency of a known single nucleotide polymorphism (R495Q) was not significantly different between patients and controls. Conclusion –  The results indicate that the DCTN1 gene is probably not influencing susceptibility to neurodegeneration in MS.

  • heterozygous r1101k mutation of the DCTN1 gene in a family with als and ftd
    Annals of Neurology, 2005
    Co-Authors: C Munch, Reinhard Sedlmeier, Thomas Meyer, Annedorte Sperfeld, Angela Rosenbohm, Ingo Uttner, Sven N Reske, Bernd J Krause, C O Hanemann
    Abstract:

    A heterozygous R1101K mutation of the p150 subunit of dynactin (DCTN1) is reported in a family with amyotrophic lateral sclerosis (ALS) and co-occurrence of frontotemporal dementia (FTD). Two members of our kindred were affected with motor neuron disease and two with dementia in an autosomal dominant pattern of inheritance. We excluded the involvement of the ALS and FTD-linked genes for copper/zinc superoxide dismutase (SOD1) and tau. The R1101K sequence alteration of the DCTN1 gene may predispose subjects to ALS and FTD.

  • point mutations of the p150 subunit of dynactin DCTN1 gene in als
    Neurology, 2004
    Co-Authors: C Munch, Reinhard Sedlmeier, Thomas Meyer, V Homberg, Annedorte Sperfeld, A Kurt, Johannes Prudlo, G Peraus, C O Hanemann, G Stumm
    Abstract:

    The authors report mutation screening of the p150 subunit of dynactin (DCTN1) and the cytoplasmic dynein heavy chain (DNCHC1) genes in 250 patients with ALS and 150 unrelated control subjects. Heterozygous missense mutations of the DCTN1 gene were detected in one apparently sporadic case of ALS (T1249I), one individual with familial ALS (M571T), two patients with familial ALS, and two unaffected relatives in the same kindred (R785W). The allelic variants of the DCTN1 gene may represent a previously unknown genomic risk factor for ALS.